Separate and interacting effects of the endogenous circadian system and behaviors on plasma aldosterone in humans.

Measurements of aldosterone for diagnosis of primary aldosteronism are usually made from blood sampled in the morning when aldosterone typically peaks. We tested the relative contributions and interacting influences of the circadian system, ongoing behaviors, and prior sleep to this morning peak in aldosterone. To determine circadian rhythmicity and separate effects of behaviors on aldosterone, 16 healthy participants completed a 5-day protocol in dim light while all behaviors ranging from sleep to exercise were standardized and scheduled evenly across the 24-h circadian period. In another experiment, to test the separate effects of prior nocturnal sleep or the inactivity that accompanies sleep on aldosterone, 10 healthy participants were studied across 2 nights: 1 with sleep and 1 with maintained wakefulness (randomized order). Plasma aldosterone was measured repeatedly in each experiment. Aldosterone had a significant endogenous rhythm ( P < 0.001), rising across the circadian night and peaking in the morning (~8 AM). Activity, including exercise, increased aldosterone, and different behaviors modulated aldosterone differently across the circadian cycle (circadian phase × behavior interaction; P < 0.001). In the second experiment, prior nocturnal sleep and prior rested wakefulness both increased plasma aldosterone ( P < 0.001) in the morning, to the same extent as the change in circadian phases between evening and morning. The morning increase in aldosterone is due to effects of the circadian system plus increased morning activities and not prior sleep or the inactivity accompanying sleep. These findings have implications for the time of and behaviors preceding measurement of aldosterone, especially under conditions of shift work and jet lag.

When to Stop Eculizumab in Complement-Mediated Thrombotic Microangiopathies.

The terminal complement-inhibitor eculizumab has dramatically changed the management of patients with atypical hemolytic uremic syndrome (aHUS), and has also shown promise for treating certain forms of secondary HUS (sHUS), including that caused by drugs and solid-organ/hematopoietic stem cell transplant. While effective, eculizumab is costly and inconvenient. In this review, we evaluate the literature on eculizumab cessation in these diseases to better inform clinicians who consider stopping therapy. Reported relapse rates in aHUS after stopping eculizumab are as high as 30%, suggesting indefinite therapy is reasonable and that patients who choose to stop should be closely monitored. In sHUS, relapse is rare, justifying short courses of eculizumab.

Silicate nephrolithiasis after ingestion of supplements containing silica dioxide.

Silicate calculi are common in some mammals, such as dogs and sheep, but extremely rare in humans. We report a case of silicate calculi in a woman using oral over-the-counter Uncaria tomentosa, Digestive Advantage and FlexProtex supplements. All 3 contained the excipient silica dioxide. Stone analysis showed composition of 100% silicate. The nephrolithiasis promptly abated after discontinuation of the products containing silica, then returned when the patient restarted her supplements. This case emphasizes the importance of stone analysis when obvious causes of nephrolithiasis are unclear and highlights the concerns of using over-the-counter supplements without substantial oversight.